Dupilumab Induced Limbal Stem Cell Deficiency

Mehta, Urmi; Farid, Marjan

doi:10.2147/imcrj.s308583

Cited by 15 publications

(16 citation statements)

References 13 publications

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“…There were 13 cases of DIOSD reported in the literature, [61][62][63][64][65][66][67][68][69][70][71][72] six of which required dupilumab discontinuation due to ocular discomfort, and the symptomatology subsequently improved. In one case, however, dupilumab frequency of administration was reduced from biweekly to every 4 weeks, in this case, also, with significant ocular improvement.…”

Section: Case Reportsmentioning

confidence: 99%

“…All DIOSD cases were diagnosed by an ophthalmologist and seven cases were mild, five were moderate, and one was a severe form. Six patients had previous ocular disease, either dry eyes 61,72 allergic conjunctivitis, 68 trauma induced corneal flap removal, 67 keratoconus, 66 or repeated episodes of infectious conjunctivitis, keratitis, and cataract. 63 Treatment methods employed were artificial tears, 68,72 hyaluronic acid/carbomer eye drops, 73 autologous serum eyedrops, 67 corticosteroid eyedrops, 62,[64][65][66][67][68][69][70]73 cyclosporine eye drops, 64,68,72 antibiotic, 66,73 tacrolimus, 73 lifitegrast drops, 72 and surgery 63,69 (Tables 4 and 5).…”

Section: Case Reportsmentioning

confidence: 99%

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Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Neagu

Dianzani

Avallone

et al. 2022

Acad Dermatol Venereol

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Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be managed with topical treatments, moderate‐to‐severe forms require systemic therapies. Dupilumab is the first human monoclonal antibody approved for the treatment of AD. Its action is through IL‐4 receptor alpha subunit inhibition, thus blocking IL‐4 and IL‐13 signaling pathways. It has been shown to be an effective, well‐tolerated therapy for AD, as well as for asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and eosinophilic esophagitis (EoE). However, an increasing incidence of dupilumab‐induced ocular surface disease (DIOSD) has been reported in patients treated with dupilumab, as compared to placebo. The aim of this study was to summarize scientific data regarding DIOSD in AD patients treated with dupilumab. A search of PubMed and clinicaltrials.gov databases was performed. There was no limit to study design. All AD cases were moderate‐to‐severe. DIOSD was either dermatologist‐, allergist‐, or ophthalmologist‐assessed. Evidence shows that DIOSD occurs most frequently in patients with atopic dermatitis and not in other skin conditions, neither in patients with asthma, CRSwNP, nor EoE who are on dupilumab treatment. Further studies are warranted in order to establish a causal relationship between dupilumab and ocular surface disease. Nevertheless, ophthalmological evaluations prior to dupilumab initiation can benefit AD patients with previous ocular pathology or current ocular symptomatology. Also, patch testing for ocular allergic contact dermatitis might be advantageous in patients with a history of allergic conjunctivitis. Furthermore, TARC, IgE, and circulating eosinophils levels might be important biomarkers for a baseline assessment of future candidates to dupilumab treatment. However, TARC measurements should be resumed for research purposes only.

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Section: Case Reportsmentioning

confidence: 99%

Section: Case Reportsmentioning

confidence: 99%

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Neagu

Dianzani

Avallone

et al. 2022

Acad Dermatol Venereol

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“… 3 A similar increase was not found in patients treated with dupilumab with other diseases. 3 Additionally, 23 of 85 patients (27%) developed ocular surface disease while on dupilumab 4 and case reports have described different instances of blepharoconjunctivitis, 5 cicatricial ectropion, 6 nodular swelling of the limbus, 7–10 cicatricial conjunctivitis, 11 punctal stenosis, 12 13 proliferative conjunctivitis, 14 episcleritis 15 and corneal ulceration 16 17 under dupilumab treatment.…”

Section: Introductionmentioning

confidence: 99%

Characterising the chronicity of dupilumab-associated ocular surface disease: an analysis of a retrospective case series

Hébert

You

et al. 2022

BMJ Open Ophth

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Background/aimsTo describe the clinical presentation and treatment response of dupilumab-associated ocular surface disease (DAOSD).MethodsThis is a retrospective case series of atopic dermatitis patients with DAOSD treated with dupilumab. All consecutive patients with atopic dermatitis referred by dermatologists for suspicion of DAOSD between May 2018 and June 2020 were systemically assessed by a single ophthalmologist. Presenting signs of DAOSD, duration of treatment and associated response are described.ResultsTwenty-eight patients had DAOSD during the study period. Average age was 45.6±14.8 years and 13 (46%) were female. Average follow-up was 15±10 months. Most presentations consisted in diffuse, inflammatory conjunctivitis (n=19, 68%). Other signs included peripheral corneal infiltrates (n=7, 25%), limbal nodules (n=7, 25%) and dry eye syndrome (n=6, 21%). To control ocular symptoms, tapering of corticosteroid eyedrops was slow: taper duration of strong and mild corticosteroid eyedrops averaged 10±8 weeks and 49±34 weeks, respectively. Four patients (14%) required an increase of corticosteroid eyedrops during taper due to clinical deterioration. Corticosteroid eyedrops were still required at final follow-up among 10 patients (36%). Dupilumab was temporarily stopped in 3 patients (11%), one of which did not wish to resume dupilumab for unrelated reasons. Symptomatic improvement and/or complete resolution was achieved in 25/26 patients at follow-up (96%) with empirical treatment.ConclusionsDAOSD may follow the course of a chronic illness. Long-term corticosteroid eyedrops were required in many patients and when taper was possible, this was done after a prolonged treatment duration. Most patients’ ocular symptoms could be controlled, allowing dupilumab continuation.

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“…Upwards of 25% of patients receiving dupilumab suffer from this condition, and symptoms appear after six months of dupilumab use [ 6 , 7 ]. IL-13 has been shown to stimulate goblet cells, and inhibiting its function can lead to hypoplasia or complete absence of these cells in dupilumab patients [ 8 , 9 , 10 ]. Goblet cell dysfunction causes decreased mucin on the ocular surface.…”

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confidence: 99%

Corneal Refractive Surgery Considerations in Patients on Dupilumab

Moshirfar

Seitz

Ply

et al. 2022

JCM

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Dupilumab is a biologic approved by the United States Food and Drug Administration (US FDA) for the treatment of atopic dermatitis. While it is an effective medication for eczema, ocular side effects are common in patients receiving dupilumab therapy. Greater consideration is needed when evaluating these individuals for corneal refractive surgery. Dupilumab patients may suffer from atopy, a condition that also merits consideration in those desiring refractive surgery. Additional testing and careful consideration are needed, as these patients have an increased risk of dry eye syndrome, keratoconus, cataracts, diffuse lamellar keratitis, viral keratitis, and perioperative infection. This commentary discusses the current understanding of dupilumab ocular side effects and investigates factors to consider when evaluating these patients for corneal refractive surgery.

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Dupilumab Induced Limbal Stem Cell Deficiency

Cited by 15 publications

References 13 publications

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review

Characterising the chronicity of dupilumab-associated ocular surface disease: an analysis of a retrospective case series

Corneal Refractive Surgery Considerations in Patients on Dupilumab

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